Food Therapy IFood Therapy IFood Therapy IFood Therapy IDr. Alex AlexanderWeek 1, Fall 2012

For Use With Video Lecture

Dr. Alex AlexanderWeek 1, Fall 2012

For Use With Video Lecture

VITAMINSVITAMINS

What Are They?What Are They?

• Definitions of vitamins & functions (in general) Definition: organic nutrients required in

minute amounts to perform specific functions Functions:

o Coenzymes—precursors to, or components ofo Metabolic pathways—many involved ino Normal metabolism—vitamins required foro Essential nutrients to meet normal physiological needs—cannot

be synthesized by the body in adequate amounts otherwiseo Normal bodily functions (maintenance, growth, development,

and/or production)—required usually in minute amountso Specific deficiency syndromes result in their absence or under-

utilization

• Definitions of vitamins & functions (in general) Definition: organic nutrients required in

minute amounts to perform specific functions Functions:

o Coenzymes—precursors to, or components ofo Metabolic pathways—many involved ino Normal metabolism—vitamins required foro Essential nutrients to meet normal physiological needs—cannot

be synthesized by the body in adequate amounts otherwiseo Normal bodily functions (maintenance, growth, development,

and/or production)—required usually in minute amountso Specific deficiency syndromes result in their absence or under-

utilization

Their NamesTheir Names• A E D K = Fat Soluble, Vitamin C & the Bs =Water

Soluble

• B1, B2, B3, B5, B6, B7, B9, B12, Thiamine, Riboflavin, Niacin, Pantothenic, Pyridoxine, Biotin, Folic Acid, Cyanocobalamin,

■ Vitamin B1 (thiamine)

■ Vitamin B2 (riboflavin)■ Vitamin B3 (niacin or niacinamide)■ Vitamin B5 (pantothenic acid)■ Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride)■ Vitamin B7 (biotin)■ Vitamin B9 (folic acid)■ Vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin

supplements)

• A E D K = Fat Soluble, Vitamin C & the Bs =Water Soluble

• B1, B2, B3, B5, B6, B7, B9, B12, Thiamine, Riboflavin, Niacin, Pantothenic, Pyridoxine, Biotin, Folic Acid, Cyanocobalamin,

■ Vitamin B1 (thiamine)

■ Vitamin B2 (riboflavin)■ Vitamin B3 (niacin or niacinamide)■ Vitamin B5 (pantothenic acid)■ Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine, or pyridoxine hydrochloride)■ Vitamin B7 (biotin)■ Vitamin B9 (folic acid)■ Vitamin B12 (various cobalamins; commonly cyanocobalamin in vitamin

supplements)

Week 1 Lecture Includes:Week 1 Lecture Includes:

• Deficiency and loss in processing

• Assessing patient status considerations

• Vitamin A, Beta Carotene and Lycopene

• Thiamine-B1, Riboflavin-B2, Niacin-B3

• Biochemistry, Indications, Dose and Toxicity

• Deficiency and loss in processing

• Assessing patient status considerations

• Vitamin A, Beta Carotene and Lycopene

• Thiamine-B1, Riboflavin-B2, Niacin-B3

• Biochemistry, Indications, Dose and Toxicity

Deficiency?Deficiency?• General classification of malnutrition and potential

causes of primary and secondary deficiencies. Definition of malnutrition is either too little or too much nutrient intake According to Stedman’s: “Faulty nutrition resulting from malassimilation, poor diet, or overeating.”

There are six classifications of malnutrition:1) Cause: Primary (exogenous) or Secondary (endogenous)2) Type: Excess/toxicity (overnutrition) or Deficiency (undernutrition) and may see same Sx’s for both3) Nutrients: Vitamins, Minerals, Proteins, energy (CHO, Fat or Protein)4) Degree: Mild – Moderate – Severe which can range from Depleted stores to Biochemical lesion to functional change (eg. Fe deficiency)5) Duration: Acute, Sub-acute, and chronic6) Outcome: Reversible, irreversible

• General classification of malnutrition and potential causes of primary and secondary deficiencies.

Definition of malnutrition is either too little or too much nutrient intake According to Stedman’s: “Faulty nutrition resulting from malassimilation, poor diet, or overeating.”

There are six classifications of malnutrition:1) Cause: Primary (exogenous) or Secondary (endogenous)2) Type: Excess/toxicity (overnutrition) or Deficiency (undernutrition) and may see same Sx’s for both3) Nutrients: Vitamins, Minerals, Proteins, energy (CHO, Fat or Protein)4) Degree: Mild – Moderate – Severe which can range from Depleted stores to Biochemical lesion to functional change (eg. Fe deficiency)5) Duration: Acute, Sub-acute, and chronic6) Outcome: Reversible, irreversible

More on MalnutritionMore on Malnutrition

Potential causes of Primary deficiencies stem from psychosocial and technological causes including poor food habits, poverty, ignorance, lack of vitamin-rich food (consumption of highly refined foods), lack of total food, vitamin destruction (storage, processing, cooking), anorexia (homebound elderly, dental problems, chemo pts), food taboos and fads, apathy, drug and radiation therapies.

Potential causes of Primary deficiencies stem from psychosocial and technological causes including poor food habits, poverty, ignorance, lack of vitamin-rich food (consumption of highly refined foods), lack of total food, vitamin destruction (storage, processing, cooking), anorexia (homebound elderly, dental problems, chemo pts), food taboos and fads, apathy, drug and radiation therapies.

Secondary CausesSecondary Causes

Secondary causes stem from biological factors such as poor digestion (achlorhydria), malabsorption (impaired intestinal fxn d/t infxn, parasites, pancreatitis or dysbiosis), impaired metabolic utilization (drug therapies), increased metabolic need (pregnancy, lactation, rapid growth, infxn, nutrient imbalance), increased vitamin excretion (diuresis, lactation, excess sweating).

Secondary causes stem from biological factors such as poor digestion (achlorhydria), malabsorption (impaired intestinal fxn d/t infxn, parasites, pancreatitis or dysbiosis), impaired metabolic utilization (drug therapies), increased metabolic need (pregnancy, lactation, rapid growth, infxn, nutrient imbalance), increased vitamin excretion (diuresis, lactation, excess sweating).

Steps to AvitaminosisSteps to Avitaminosis

• Dietary intake (diet hx) + 2º conditioning factors----> Gradual decrease in tissue levels (blood, urine, tissue analysis)---->Biochemical lesions (reduced enzymes, altered metabolites)---->Anatomic lesions (clinical evalutation)---->Pathology—dz (clinical sx)

• Dietary intake (diet hx) + 2º conditioning factors----> Gradual decrease in tissue levels (blood, urine, tissue analysis)---->Biochemical lesions (reduced enzymes, altered metabolites)---->Anatomic lesions (clinical evalutation)---->Pathology—dz (clinical sx)

Compare Water and Fat SolCompare Water and Fat Sol4. Compare water and fat-soluble vitamins (in

general) with regard to absorption, transport, storage, excretion, toxicity and requirements. Water Soluble (B & C) Fat Soluble (ADEK)

Absorption Blood Lymph →Blood

Transport Travel freely May require protein carrier

Storage Freely circulate in water Cells associated with fat

Excretion Kidney removes excess Less readily excreted, remain in fat continued storage sites

Toxicity Unlikely to reach toxic levels Likely to reach toxic levels

Requirement Frequent, small amount Periodic amount

4. Compare water and fat-soluble vitamins (in general) with regard to absorption, transport, storage, excretion, toxicity and requirements. Water Soluble (B & C) Fat Soluble (ADEK)

Absorption Blood Lymph →Blood

Transport Travel freely May require protein carrier

Storage Freely circulate in water Cells associated with fat

Excretion Kidney removes excess Less readily excreted, remain in fat continued storage sites

Toxicity Unlikely to reach toxic levels Likely to reach toxic levels

Requirement Frequent, small amount Periodic amount

Screening Clients/PatientsScreening Clients/Patients• When screening a client’s diet regarding

vitamin content, what point to keep in mind?5 points:1) Amount of vitamin expected to be in the food2) Quantity of the food that is actually eaten3) Frequency of food that is eaten4) Stability of the vitamin during process &

cooking5) Bioavailability and amount needed of the

vitamin, especially when ingested with other foods or dietary supplements.

• When screening a client’s diet regarding vitamin content, what point to keep in mind?

5 points:1) Amount of vitamin expected to be in the food2) Quantity of the food that is actually eaten3) Frequency of food that is eaten4) Stability of the vitamin during process &

cooking5) Bioavailability and amount needed of the

vitamin, especially when ingested with other foods or dietary supplements.

What About Vitamin Loss in Foods?What About Vitamin Loss in Foods?What techniques needed (storage and preparation) to reduce vitamin losses from foods?1)Consume soon after harvesting or purchasing.2)Refrigerate fresh produce, wrap tight to retain moisture & decrease exposure to air.3)For longer storage, freezing better. Blanch first to retain flavor and stop enzymes that destroy vitamins.4)Wait til the last minute to cut up food for a meal. The smaller the pieces that food is cut into, the > the nutrient loss d/t exposure to light and oxygen.5)Higher the temp. & length of cooking → the > losses. Use low temp for short time, but long & hot enough to ensure safety.6)Microwaving uses shorter cooking times, so may result in > nutrient retention in some cases.•Water-soluble nutrients are lost in water, so avoid soaking and cook veg. in skins.1)Cook frozen veg. w/out thawing.2)Do NOT add baking soda to vegetable cooking water.3)Use techniques that do not bring veg. into contact with water (steaming, pressure cooking, dry heat, roasting, grilling, stir-frying or baking).

What techniques needed (storage and preparation) to reduce vitamin losses from foods?1)Consume soon after harvesting or purchasing.2)Refrigerate fresh produce, wrap tight to retain moisture & decrease exposure to air.3)For longer storage, freezing better. Blanch first to retain flavor and stop enzymes that destroy vitamins.4)Wait til the last minute to cut up food for a meal. The smaller the pieces that food is cut into, the > the nutrient loss d/t exposure to light and oxygen.5)Higher the temp. & length of cooking → the > losses. Use low temp for short time, but long & hot enough to ensure safety.6)Microwaving uses shorter cooking times, so may result in > nutrient retention in some cases.•Water-soluble nutrients are lost in water, so avoid soaking and cook veg. in skins.1)Cook frozen veg. w/out thawing.2)Do NOT add baking soda to vegetable cooking water.3)Use techniques that do not bring veg. into contact with water (steaming, pressure cooking, dry heat, roasting, grilling, stir-frying or baking).

Define Vitamins Again?Define Vitamins Again?

Definition: organic, essential nutrient required in small amount to perform specific function that promotes growth, reproduction and maintenance of bodyFunction: precursors to or of co-enzyme; metabolic pathways; normal bodily function (reproduction, growth, maintenance)

Definition: organic, essential nutrient required in small amount to perform specific function that promotes growth, reproduction and maintenance of bodyFunction: precursors to or of co-enzyme; metabolic pathways; normal bodily function (reproduction, growth, maintenance)

Deficiencies SuccinctlyDeficiencies Succinctly

Primary deficiencies* Poor food habits * poverty * lack of education/knowledge * Anorexia * food taboos & fads * vitamin destruction * apathy* Lack of total foodSecondary deficiencies* Poor digestion * malabsorption * impaired metabolic utilization* Incr. metabolic need * incr. vitamin excretion

Primary deficiencies* Poor food habits * poverty * lack of education/knowledge * Anorexia * food taboos & fads * vitamin destruction * apathy* Lack of total foodSecondary deficiencies* Poor digestion * malabsorption * impaired metabolic utilization* Incr. metabolic need * incr. vitamin excretion

The Vitamins - Recall that the recommended

level is often like the minimum wage - just enough to live on

The Vitamins - Recall that the recommended

level is often like the minimum wage - just enough to live on

1968- NOW1968- NOW

The Fat Soluble VitaminsThe Fat Soluble Vitamins

• A E D K• A E D K

VITAMIN AVITAMIN A

Biochemistry: Vitamin A promotes differentiation of epithelial tissues. Vitamin A controls expression of other genes. Vitamin A is a component of visual purple→involved in light (not color) reception→Vit A deficiency shows up as night blindness. Vitamin A deficiency impairs secretory IgA response (immune).

Biochemistry: Vitamin A promotes differentiation of epithelial tissues. Vitamin A controls expression of other genes. Vitamin A is a component of visual purple→involved in light (not color) reception→Vit A deficiency shows up as night blindness. Vitamin A deficiency impairs secretory IgA response (immune).

Vitamin AVitamin A

Vit A is found in animal foods. Never found pre-formed in plants. Vitamin A receptor sits on DNA and increases or decreases translation of certain genes. Vit A receptor appears to be important in controlling genes for steroid hormones.

Vit A is found in animal foods. Never found pre-formed in plants. Vitamin A receptor sits on DNA and increases or decreases translation of certain genes. Vit A receptor appears to be important in controlling genes for steroid hormones.

Indications- Vit AIndications- Vit AImmune function: Supplementation of malnourished children with vitamin A reduces mortality from measles and diarrhea (most studies done looking at Vit A use in acute infxns were done in 3rd world countries and may not be applicable to 1st world since deficiencies may exist in these malnourished populations that do not exist in the 1st world).

The American Academy of Pediatrics recommends vitamin A supplementation during measles infection. Most research in the developed world suggests little, if any benefit from supplementation with vitamin A during acute illness. Some studies have even found worse outcomes in children receiving vitamin A (Pediatrics. 1998 May;101(5):E3→study done in a western population giving vit A in acute dose compared to placebo showed

worse outcomes in vit A group).

Immune function: Supplementation of malnourished children with vitamin A reduces mortality from measles and diarrhea (most studies done looking at Vit A use in acute infxns were done in 3rd world countries and may not be applicable to 1st world since deficiencies may exist in these malnourished populations that do not exist in the 1st world).

The American Academy of Pediatrics recommends vitamin A supplementation during measles infection. Most research in the developed world suggests little, if any benefit from supplementation with vitamin A during acute illness. Some studies have even found worse outcomes in children receiving vitamin A (Pediatrics. 1998 May;101(5):E3→study done in a western population giving vit A in acute dose compared to placebo showed

worse outcomes in vit A group).

Indications- Vit AIndications- Vit A

HIV support: Pregnant women with HIV infection are more likely to transmit the virus to the fetus if they have low vitamin A status. In a clinical trial, vitamin A supplementation was only effective in preventing transmission to pre-term infants, not full-term. Women w/ HIV infxn in this country tend to have other medical Hx that may predispose to Vit A deficiency (poor diets, drug use, homeless)

HIV support: Pregnant women with HIV infection are more likely to transmit the virus to the fetus if they have low vitamin A status. In a clinical trial, vitamin A supplementation was only effective in preventing transmission to pre-term infants, not full-term. Women w/ HIV infxn in this country tend to have other medical Hx that may predispose to Vit A deficiency (poor diets, drug use, homeless)

Indications- Vit AIndications- Vit AMenorrhagia: 25,000 IU of vitamin A bid for 15 days improved symptoms in 92% of women (58%

completely resolved) in an open trial. Vitamin A supplementation increased serum 17-beta-estradiol levels.* Also can use for metrorrhagia (bleeding from the uterus that is not due to menstruation). Think of Fe 1st for women w/ excessive menses. Also thyroid conditions can cause this. Think of Vit A if ferritin and thyroid are OK and no anatomical explanation. Discontinue Vit A Tx 1-2 cycles after Sx’s resolve since by definition these pts are of reproductive yrs (want avoid teratogenicity during preg). Vit A supplementation also improved hormone levels in studies.

Menorrhagia: 25,000 IU of vitamin A bid for 15 days improved symptoms in 92% of women (58%

completely resolved) in an open trial. Vitamin A supplementation increased serum 17-beta-estradiol levels.* Also can use for metrorrhagia (bleeding from the uterus that is not due to menstruation). Think of Fe 1st for women w/ excessive menses. Also thyroid conditions can cause this. Think of Vit A if ferritin and thyroid are OK and no anatomical explanation. Discontinue Vit A Tx 1-2 cycles after Sx’s resolve since by definition these pts are of reproductive yrs (want avoid teratogenicity during preg). Vit A supplementation also improved hormone levels in studies.

Indications-Vit AIndications-Vit A

Peptic ulcer: Small clinical trial showed vitamin A (150,000 IU per day x 4 wks) improved healing of peptic ulcer compared to other treatments (acid blockers) (Acta Physiol Hung. 1984;64(3-4):379-

84). Older studies have concluded that vitamin A is an effective prophylaxis for stress ulcer (physiologic stress secondary to burns→consider for burn pts).

Peptic ulcer: Small clinical trial showed vitamin A (150,000 IU per day x 4 wks) improved healing of peptic ulcer compared to other treatments (acid blockers) (Acta Physiol Hung. 1984;64(3-4):379-

84). Older studies have concluded that vitamin A is an effective prophylaxis for stress ulcer (physiologic stress secondary to burns→consider for burn pts).

Indications- Vit AIndications- Vit A

Dermatology (most common use of high dose A in allopathic medicine)

a. Acne vulgaris: In an uncontrolled trial, doses of 300,000 IU/day for teenage females and 400,000 IU/day for teenage males were used for periods of 5 months with good success in cases of severe acne, with no apparent toxicity. Lesions tended to recur after treatment was discontinued, but the severity could be minimized by use of conventional therapy, such as antibiotics. Lower doses (such as 50,000-150,000 IU/day) have not been found to be helpful. Administration of vitamin E may potentiate the therapeutic effect of vitamin A; the combination of 800 IU/day of vitamin E and 100,000 IU/day of vitamin A may be as effective as the higher doses of vitamin A alone. In more severe cases of acne, the dosage of vitamin E may be increased to 1,200-1,600 IU/day along with 100,000 IU/day of vitamin A.* Synthetic vit A is used because it doesn’t store in liver as does natural forms of Vit A. Acutane (Rx) works for some people but people don’t like it because it’s a teratogen and can cause acute liver toxicity (even though it’s synthetic and therefore not cumulative) and nausea. Natural Vit A is slightly less effective than acutane. Mechanism not known (maybe hormone regulation or ↓ sebum production??)

Dermatology (most common use of high dose A in allopathic medicine)

a. Acne vulgaris: In an uncontrolled trial, doses of 300,000 IU/day for teenage females and 400,000 IU/day for teenage males were used for periods of 5 months with good success in cases of severe acne, with no apparent toxicity. Lesions tended to recur after treatment was discontinued, but the severity could be minimized by use of conventional therapy, such as antibiotics. Lower doses (such as 50,000-150,000 IU/day) have not been found to be helpful. Administration of vitamin E may potentiate the therapeutic effect of vitamin A; the combination of 800 IU/day of vitamin E and 100,000 IU/day of vitamin A may be as effective as the higher doses of vitamin A alone. In more severe cases of acne, the dosage of vitamin E may be increased to 1,200-1,600 IU/day along with 100,000 IU/day of vitamin A.* Synthetic vit A is used because it doesn’t store in liver as does natural forms of Vit A. Acutane (Rx) works for some people but people don’t like it because it’s a teratogen and can cause acute liver toxicity (even though it’s synthetic and therefore not cumulative) and nausea. Natural Vit A is slightly less effective than acutane. Mechanism not known (maybe hormone regulation or ↓ sebum production??)

Indications- Vit AIndications- Vit A

Dermatology, Continued

a.Darier's disease (keratosis follicularis): 200,000 IU/day of vitamin A or the vitamin A/vitamin E protocol, as described for acne, may be beneficial (case reports).*b.Seborrheic keratoses or senile keratoses responded to 100,000 IU/day of vitamin A for a mean treatment period of 19.8 months (uncontrolled trial). Lesions disappeared in 26% of 50 cases, with an additional 64% showing improvement.* Use cod liver oil as Vit A source. c.Eczema: At a dose of 25,000 to 200,000 IU/day for 3-21 months, vitamin A produced marked improvement in eczema in 6 of 9 children, without causing side effects (uncontrolled trial).* Also a study that used topical vitamin A. Cod liver oil works really well for dyshidrotic eczema (conventional Tx’s don’t work well for this)d.Follicular hyperkeratosis: a condition of squamous metaplasia of the sebaceous glands, which some sources report is due to vitamin A deficiency.

Dermatology, Continued

a.Darier's disease (keratosis follicularis): 200,000 IU/day of vitamin A or the vitamin A/vitamin E protocol, as described for acne, may be beneficial (case reports).*b.Seborrheic keratoses or senile keratoses responded to 100,000 IU/day of vitamin A for a mean treatment period of 19.8 months (uncontrolled trial). Lesions disappeared in 26% of 50 cases, with an additional 64% showing improvement.* Use cod liver oil as Vit A source. c.Eczema: At a dose of 25,000 to 200,000 IU/day for 3-21 months, vitamin A produced marked improvement in eczema in 6 of 9 children, without causing side effects (uncontrolled trial).* Also a study that used topical vitamin A. Cod liver oil works really well for dyshidrotic eczema (conventional Tx’s don’t work well for this)d.Follicular hyperkeratosis: a condition of squamous metaplasia of the sebaceous glands, which some sources report is due to vitamin A deficiency.

Indications- Vit AIndications- Vit A

Wound healing: Animal studies have shown supplementation with vitamin A to speed wound healing, but no human studies are available to confirm this. Vitamin A is a part of the post-surgical protocol of many naturopathic physicians, but its use remains theoretical.

Wound healing: Animal studies have shown supplementation with vitamin A to speed wound healing, but no human studies are available to confirm this. Vitamin A is a part of the post-surgical protocol of many naturopathic physicians, but its use remains theoretical.

Indications - Vit AIndications - Vit A

1)Tx of pre-Cancerous Conditions: a.Cervical dysplasia- Vit A is part of the protocol used

along w/ escharotic Tx for cervical dysplasia and carcinoma described in an article published in the Journal of Naturopathic Medicine. In addition to escharotic Tx and Vit A suppositories they used, botanical tinctures, vitamin C, beta carotene, and dietary changes with added therapies of lomatium, folic acid, selenium.

b.Acute promylocytic leukemia- preleukemic condition that will reliably go into remission w/ high dose Vit A (up to 1 million IU/wk)

1)Tx of pre-Cancerous Conditions: a.Cervical dysplasia- Vit A is part of the protocol used

along w/ escharotic Tx for cervical dysplasia and carcinoma described in an article published in the Journal of Naturopathic Medicine. In addition to escharotic Tx and Vit A suppositories they used, botanical tinctures, vitamin C, beta carotene, and dietary changes with added therapies of lomatium, folic acid, selenium.

b.Acute promylocytic leukemia- preleukemic condition that will reliably go into remission w/ high dose Vit A (up to 1 million IU/wk)

DOSAGE - Vit ADOSAGE - Vit A

Dosage: RDA = 2667 IU for women, 3300 IU for men. Studies have tended to use doses between 5-25,000 IU for long term treatment, but have gone up as high as several hundred thousand IU for short periods of time. A water soluble form of vitamin A called retinyl palmitate is available, and may be the preferred form for patients with fat-malnutrition (cystic fibrosis, crohns, chronic pancreatitis, chemo pts,).

Dosage: RDA = 2667 IU for women, 3300 IU for men. Studies have tended to use doses between 5-25,000 IU for long term treatment, but have gone up as high as several hundred thousand IU for short periods of time. A water soluble form of vitamin A called retinyl palmitate is available, and may be the preferred form for patients with fat-malnutrition (cystic fibrosis, crohns, chronic pancreatitis, chemo pts,).

ToxicityToxicityToxicity: Overdose may cause liver damage, pseudotumor cerebri (having all the Sx’s of a brain tumor (i.e. HA, neurologic changes, papillary edema) w/o actually having a brain tumor), or death. Doses of 300,000 IU/day for females and 400,000-500,000 IU/day for males have been well tolerated for 5 months by teenagers with acne.

Dosages of 50,000 IU/day for 18 months have caused toxicity in some adults w/ acne (tolerated well). Alcoholics, elderly individuals, and patients with liver disease have increased susceptibility to vitamin A toxicity.*

One study found no evidence of detrimental effects from 25,000 IU/day of vitamin A for up to 12 years (these pts were Treated for retinitis pigmentosa and had no liver toxicity).(PMID: 10197566, Am J Clin Nutr. 1999 Apr;69(4):656-63) 25,000IU’s/day is currently considered the safe upper limit for long-term supplementation of Vit A.

Toxicity: Overdose may cause liver damage, pseudotumor cerebri (having all the Sx’s of a brain tumor (i.e. HA, neurologic changes, papillary edema) w/o actually having a brain tumor), or death. Doses of 300,000 IU/day for females and 400,000-500,000 IU/day for males have been well tolerated for 5 months by teenagers with acne.

Dosages of 50,000 IU/day for 18 months have caused toxicity in some adults w/ acne (tolerated well). Alcoholics, elderly individuals, and patients with liver disease have increased susceptibility to vitamin A toxicity.*

One study found no evidence of detrimental effects from 25,000 IU/day of vitamin A for up to 12 years (these pts were Treated for retinitis pigmentosa and had no liver toxicity).(PMID: 10197566, Am J Clin Nutr. 1999 Apr;69(4):656-63) 25,000IU’s/day is currently considered the safe upper limit for long-term supplementation of Vit A.

ToxicityToxicity

Early warning signs of vitamin A toxicity include fatigue, headache, joint pain, muscle aches, bone pain, and dry skin. These side effects are reversible upon discontinuation of the vitamin. Patients receiving high doses of vitamin A should have periodic measurement of serum calcium and aminotransferases (liver enzymes).

Early warning signs of vitamin A toxicity include fatigue, headache, joint pain, muscle aches, bone pain, and dry skin. These side effects are reversible upon discontinuation of the vitamin. Patients receiving high doses of vitamin A should have periodic measurement of serum calcium and aminotransferases (liver enzymes).

Not For Pregnant WomenNot For Pregnant WomenAdministration of massive doses of vitamin A is teratogenic in animals. The safe dose of vitamin A during pregnancy is not known. An epidemiological study suggested that intake of more than 10,000 IU/day (from supplements, but not from food) during pregnancy increases the risk of birth defects originating from the neural crest. However, in another study, ingestion of more than 10,000 IU/day was associated with a reduced risk of such birth defects. Until more is known, it appears best to avoid high-dose vitamin A in pregnant women.

Administration of massive doses of vitamin A is teratogenic in animals. The safe dose of vitamin A during pregnancy is not known. An epidemiological study suggested that intake of more than 10,000 IU/day (from supplements, but not from food) during pregnancy increases the risk of birth defects originating from the neural crest. However, in another study, ingestion of more than 10,000 IU/day was associated with a reduced risk of such birth defects. Until more is known, it appears best to avoid high-dose vitamin A in pregnant women.

Beta Carotene - Precursor to Vitamin ABeta Carotene - Precursor to Vitamin A• Biochemistry: Beta-carotene can act as a precursor

to vitamin A. It is an antioxidant and may improve immune function in some people. Supplemental beta-carotene tends to be all-trans isomer, while naturally occurring beta-carotene is a mixture of cis- and trans-isomers. The natural source beta-carotene is thought to be a better antioxidant than the all-trans synthetic version (Am J Clin Nutr. 1996 May;63(5):729-

34).

2 Vit A’s = 1 beta-carotene. Beta-carotene can be cleaved into Vit A. However, not all carotenes can be broken down into Vit A.

• Biochemistry: Beta-carotene can act as a precursor to vitamin A. It is an antioxidant and may improve immune function in some people. Supplemental beta-carotene tends to be all-trans isomer, while naturally occurring beta-carotene is a mixture of cis- and trans-isomers. The natural source beta-carotene is thought to be a better antioxidant than the all-trans synthetic version (Am J Clin Nutr. 1996 May;63(5):729-

34).

2 Vit A’s = 1 beta-carotene. Beta-carotene can be cleaved into Vit A. However, not all carotenes can be broken down into Vit A.

The Beta Carotene IsomersThe Beta Carotene IsomersThe synthetic all trans form may not be helpful clinically. When recommending beta-carotene supplementation, think natural source which also contains mixed carotenes (several isomers of several carotenes such as lycopene, beta and alpha, etc). Generally, doses of 15mg beta-carotene from a mixed source are adequate.

Side note: In general the body cares a lot about isomer forms. For example the body uses only the L form of all amino acids (w/ one exception).

The synthetic all trans form may not be helpful clinically. When recommending beta-carotene supplementation, think natural source which also contains mixed carotenes (several isomers of several carotenes such as lycopene, beta and alpha, etc). Generally, doses of 15mg beta-carotene from a mixed source are adequate.

Side note: In general the body cares a lot about isomer forms. For example the body uses only the L form of all amino acids (w/ one exception).

Indications - Beta CaroteneIndications - Beta Carotene

1)Precancerous lesions: Supplementation with 60 mg/day of beta-carotene for 6 months induced regression of oral leukoplakia in 52% of 54 patients (uncontrolled trial).* Effect appears to be lasting- at least up to 1yr (PMID: 10604407, Arch Otolaryngol Head Neck Surg. 1999 Dec;125(12):1305-

10). In a small trial, supplementation with natural beta-carotene led to regression of precancerous stomach lesions. Synthetic beta-carotene was ineffective. This is the only study that compared natural vs synthetic forms.

2)Asthma: supplementation with 64 mg of natural source beta-carotene for one week reduced symptoms of exercise-induced asthma.*(PMID: 10400482, Ann Allergy Asthma Immunol. 1999 Jun;82(6):549-53) 80% of pts w/ asthma are made worse w/ exercise. Oxidants are the trigger for exercise induced asthma. Leukotrienes are the trigger in non-exercise induced asthma.

3)Skin eruptions: In uncontrolled trials, patients with erythropoietic porphyria or polymorphous light eruption showed reduced sensitivity to sunlight after treatment with 50-200 mg/day of beta-carotene.

4)Stimulation of immune function: small studies w/ people w/ HIV. Probably not true for immune competent individuals.

1)Precancerous lesions: Supplementation with 60 mg/day of beta-carotene for 6 months induced regression of oral leukoplakia in 52% of 54 patients (uncontrolled trial).* Effect appears to be lasting- at least up to 1yr (PMID: 10604407, Arch Otolaryngol Head Neck Surg. 1999 Dec;125(12):1305-

10). In a small trial, supplementation with natural beta-carotene led to regression of precancerous stomach lesions. Synthetic beta-carotene was ineffective. This is the only study that compared natural vs synthetic forms.

2)Asthma: supplementation with 64 mg of natural source beta-carotene for one week reduced symptoms of exercise-induced asthma.*(PMID: 10400482, Ann Allergy Asthma Immunol. 1999 Jun;82(6):549-53) 80% of pts w/ asthma are made worse w/ exercise. Oxidants are the trigger for exercise induced asthma. Leukotrienes are the trigger in non-exercise induced asthma.

3)Skin eruptions: In uncontrolled trials, patients with erythropoietic porphyria or polymorphous light eruption showed reduced sensitivity to sunlight after treatment with 50-200 mg/day of beta-carotene.

4)Stimulation of immune function: small studies w/ people w/ HIV. Probably not true for immune competent individuals.

DosageDosage

Dosage: For most individuals, 15 mg of beta-carotene (25,000 IU) should be plenty to replete a vitamin A deficiency. As the conversion of beta-carotene to vitamin A is limited, beta-carotene cannot be used to derive a high-dose vitamin A effect. There is no generally recognized maximum dose of beta-carotene.

Dosage: For most individuals, 15 mg of beta-carotene (25,000 IU) should be plenty to replete a vitamin A deficiency. As the conversion of beta-carotene to vitamin A is limited, beta-carotene cannot be used to derive a high-dose vitamin A effect. There is no generally recognized maximum dose of beta-carotene.

ToxicityToxicity• Toxicity: People taking high doses of beta-

carotene from supplements or foods can have a transient and harmless change in skin tone called carotenemia (orange skin). Although it may alarm patients, carotenemia is not a pathologic condition and will resolve quickly upon discontinuation of beta-carotene supplementation. Should warn pts ahead of time of the potential of developing carotenemia w/ beta-carotene supplementation.

• Toxicity: People taking high doses of beta-carotene from supplements or foods can have a transient and harmless change in skin tone called carotenemia (orange skin). Although it may alarm patients, carotenemia is not a pathologic condition and will resolve quickly upon discontinuation of beta-carotene supplementation. Should warn pts ahead of time of the potential of developing carotenemia w/ beta-carotene supplementation.

Smokers and Beta CaroteneSmokers and Beta Carotene• Two large clinical trials have now concluded that

smokers taking synthetic beta-carotene supplements have a higher incidence of lung cancer than those taking placebo (PMID: 8127329, N Engl J Med. 1994 Apr 14;330(15):1029-35; PMID: 8602180, N Engl J Med. 1996

May 2;334(18):1150-5). One animal study showed that beta-carotene increased the toxicity of cigarette smoke. Until more is known, smokers should not take supplemental beta-carotene (don’t assume that natural beta-carotene supplements won’t also lead to ↑ lung CA risk). High consumption of fruits and vegetables appears safe for smokers. In animal studies, beta-carotene increased the liver toxicity of alcohol (rat study).

• Two large clinical trials have now concluded that smokers taking synthetic beta-carotene supplements have a higher incidence of lung cancer than those taking placebo (PMID: 8127329, N Engl J Med. 1994 Apr 14;330(15):1029-35; PMID: 8602180, N Engl J Med. 1996

May 2;334(18):1150-5). One animal study showed that beta-carotene increased the toxicity of cigarette smoke. Until more is known, smokers should not take supplemental beta-carotene (don’t assume that natural beta-carotene supplements won’t also lead to ↑ lung CA risk). High consumption of fruits and vegetables appears safe for smokers. In animal studies, beta-carotene increased the liver toxicity of alcohol (rat study).

LycopeneLycopene• Biochemistry: Lycopene is thought to be among

the most potent antioxidants in the carotenoid family. Lycopene does not appear to have significant pro-vitamin A activity. Lycopene protects DNA against oxidative damage (although other catenoids may not). Found in saffron (highest content), tomatoes, ketchup→most red stuff. Lycopene is fat soluble. Better delivery form for lycopene in terms of tomato products are those that are more processed (paste) since the process of heating in oil liberates the lycopene.

• Biochemistry: Lycopene is thought to be among the most potent antioxidants in the carotenoid family. Lycopene does not appear to have significant pro-vitamin A activity. Lycopene protects DNA against oxidative damage (although other catenoids may not). Found in saffron (highest content), tomatoes, ketchup→most red stuff. Lycopene is fat soluble. Better delivery form for lycopene in terms of tomato products are those that are more processed (paste) since the process of heating in oil liberates the lycopene.

Indications- LycopeneIndications- Lycopene1)Prostate cancer: Epidemiologic studies have tied tomato intake to reduced intake of prostate cancer (Italian men eating tomato sauce had less prostate risk). Men with early stage prostate cancers took 30 mg of lycopene per day for three weeks had evidence of disease regression after surgery compared to those who took placebo (Exp Biol Med (Maywood). 2002 Nov;227(10):881-5). The effect of lycopene in other types of cancers has not been adequately studied.

2)Exercise induced asthma: Supplementation with 30 mg of lycopene per day for one month significantly reduced symptoms of exercise induced asthma compared to placebo (Allergy. 2000

Dec;55(12):1184-9).

1)Prostate cancer: Epidemiologic studies have tied tomato intake to reduced intake of prostate cancer (Italian men eating tomato sauce had less prostate risk). Men with early stage prostate cancers took 30 mg of lycopene per day for three weeks had evidence of disease regression after surgery compared to those who took placebo (Exp Biol Med (Maywood). 2002 Nov;227(10):881-5). The effect of lycopene in other types of cancers has not been adequately studied.

2)Exercise induced asthma: Supplementation with 30 mg of lycopene per day for one month significantly reduced symptoms of exercise induced asthma compared to placebo (Allergy. 2000

Dec;55(12):1184-9).

Dosage- LycopeneDosage- Lycopene

Dosage: Human trials have used 30 mg per day of lycopene. Optimum dose has not been determined in clinical trial.

Dosage: Human trials have used 30 mg per day of lycopene. Optimum dose has not been determined in clinical trial.

Vitamin DVitamin D

Biochemistry: Vitamin D is a hormone that is primarily responsible for regulation of calcium homeostasis. Vitamin D is also involved in differentiation of certain cell lines (stems cells to specific organ cells→kidney cell. CA cells de-differentiate). Vitamin D improves insulin sensitivity and increases insulin production in at least some patients.

Biochemistry: Vitamin D is a hormone that is primarily responsible for regulation of calcium homeostasis. Vitamin D is also involved in differentiation of certain cell lines (stems cells to specific organ cells→kidney cell. CA cells de-differentiate). Vitamin D improves insulin sensitivity and increases insulin production in at least some patients.

Vitamin D- IndicationsVitamin D- Indications

1)Prevention and treatment of osteoporosis, osteomalacia, rickets: In addition to its well known bone-preserving effect, vitamin D supplementation (800 IU/day) reduced the risk of falls by 49% in one double-blind trial. This is effect was presumably due to an improvement in balance and muscle strength resulting from vitamin D supplementation. Numerous studies have found vitamin D to be beneficial, together with calcium, for the treatment of osteoporosis. People who take vit D for prevention of osteoperosis not only have less loss in bone density, they are also less likely to fall. People who are taking vit D have better proprioreceptive sense.

1)Prevention and treatment of osteoporosis, osteomalacia, rickets: In addition to its well known bone-preserving effect, vitamin D supplementation (800 IU/day) reduced the risk of falls by 49% in one double-blind trial. This is effect was presumably due to an improvement in balance and muscle strength resulting from vitamin D supplementation. Numerous studies have found vitamin D to be beneficial, together with calcium, for the treatment of osteoporosis. People who take vit D for prevention of osteoperosis not only have less loss in bone density, they are also less likely to fall. People who are taking vit D have better proprioreceptive sense.

Vit D -IndicationsVit D -Indications

1)Psoriasis: 1,25-dihydroxyvitamin D3 (orally or topically), calcipotriol (topically) and 1alpha-hydroxyvitamin D3 (orally or topically) have each been found to be successful (uncontrolled and double-blind trials).

2)Seasonal mood disorders: Supplementation with 400 or 800 IU/day for 5 days during the winter enhanced mood in healthy student volunteers (double-blind study).

3)Malabsorption of fat soluble vitamins: People suffering from Crohn’s disease and cystic fibrosis will often require vitamin D supplementation to maintain serum levels.

1)Psoriasis: 1,25-dihydroxyvitamin D3 (orally or topically), calcipotriol (topically) and 1alpha-hydroxyvitamin D3 (orally or topically) have each been found to be successful (uncontrolled and double-blind trials).

2)Seasonal mood disorders: Supplementation with 400 or 800 IU/day for 5 days during the winter enhanced mood in healthy student volunteers (double-blind study).

3)Malabsorption of fat soluble vitamins: People suffering from Crohn’s disease and cystic fibrosis will often require vitamin D supplementation to maintain serum levels.

DOSAGE- VIT DDOSAGE- VIT D

• Dosage: For most uses, between 200 – 1000 IU are sufficient. Estimated maximum

endogenous production upon sunlight exposure is 10,000 IU per day. National Academy

of Sciences safe upper limit is 2000 IU per day. Activated forms like calcitriol are used

in much smaller doses, often less than 1 mcg per day. Patients with renal disease may

require supplementation with active form.

1,25 (D3/calcitriol) is active form. Vit d is activated in liver and kid. Consider

supplementing in kid and liv failure pts. OD of vit D→hypercalcemia→HTN,

arrhythmia, confusion (may look like a stroke). When you use the active form of vit D

you bypass the regulatory steps and have a higher risk of OD.

• Dosage: For most uses, between 200 – 1000 IU are sufficient. Estimated maximum

endogenous production upon sunlight exposure is 10,000 IU per day. National Academy

of Sciences safe upper limit is 2000 IU per day. Activated forms like calcitriol are used

in much smaller doses, often less than 1 mcg per day. Patients with renal disease may

require supplementation with active form.

1,25 (D3/calcitriol) is active form. Vit d is activated in liver and kid. Consider

supplementing in kid and liv failure pts. OD of vit D→hypercalcemia→HTN,

arrhythmia, confusion (may look like a stroke). When you use the active form of vit D

you bypass the regulatory steps and have a higher risk of OD.

Vit D ToxicityVit D Toxicity

• Toxicity: Published cases of vitamin D toxicity all involve

intakes of at least 40,000 IU/day. Calcitriol (1,25-

dihydroxyvitamin D3) should be used with caution and

monitored appropriately. Toxicity is usually due to

hypercalcemia.

• Toxicity: Published cases of vitamin D toxicity all involve

intakes of at least 40,000 IU/day. Calcitriol (1,25-

dihydroxyvitamin D3) should be used with caution and

monitored appropriately. Toxicity is usually due to

hypercalcemia.

Vitamin EVitamin E

• Biochemistry: Vitamin E is a group of eight different tocopherols or tocotrienols that

act as lipid soluble antioxidants. Most supplements contain the predominant form alpha-

tocopherol. Although some basic science research exists on the different forms of

vitamin E, the differences between the various sub-forms of vitamin E have not been

studied in humans. Vitamin E deficiency causes infertility in animal studies. There is not

known to be sn/sx’s associated w/ vit E deficiency in humans.

Most supplements that call themselves vit E are actually alpha tocopheral (may be

synthetic or natural source). Unlike beta-carotene, no research has looked at whether or

not there is a difference bwtn the different forms.

• Biochemistry: Vitamin E is a group of eight different tocopherols or tocotrienols that

act as lipid soluble antioxidants. Most supplements contain the predominant form alpha-

tocopherol. Although some basic science research exists on the different forms of

vitamin E, the differences between the various sub-forms of vitamin E have not been

studied in humans. Vitamin E deficiency causes infertility in animal studies. There is not

known to be sn/sx’s associated w/ vit E deficiency in humans.

Most supplements that call themselves vit E are actually alpha tocopheral (may be

synthetic or natural source). Unlike beta-carotene, no research has looked at whether or

not there is a difference bwtn the different forms.

Indications- Vit EIndications- Vit E

1)Cardiovascular disease (prevention and treatment):a. Myocardial infarction: Supplementation with 100-400 IU/day may reduce

the risk of myocardial infarction (double-blind trials, conflicting results, with more negative than positive results). 1st study showed a dramatic reduction in non-fatal heart attacks (didn’t protect against fatal heart attacks). Second study showed no benefit. Vit E has some nice cardiovascular actions, but it may not prevent heart attacks. Interventions like the Mediterranean or ornish diet along w/ exercise are proven to be preventative.

b. Intermittent claudication: Supplementation with 400-1,600 IU/day for at least 3 months increased walking distance (double-blind trials). IC=leg pain w/ exercise due to narrowing of arteries→arterial insufficiency of lower extremities. Stents and Pentoxifylline are conventional Tx. Vit E does work well for this. Mechanism: hypothesized having to do w/ ↓LDL oxidation or ↓platelet activation

1)Cardiovascular disease (prevention and treatment):a. Myocardial infarction: Supplementation with 100-400 IU/day may reduce

the risk of myocardial infarction (double-blind trials, conflicting results, with more negative than positive results). 1st study showed a dramatic reduction in non-fatal heart attacks (didn’t protect against fatal heart attacks). Second study showed no benefit. Vit E has some nice cardiovascular actions, but it may not prevent heart attacks. Interventions like the Mediterranean or ornish diet along w/ exercise are proven to be preventative.

b. Intermittent claudication: Supplementation with 400-1,600 IU/day for at least 3 months increased walking distance (double-blind trials). IC=leg pain w/ exercise due to narrowing of arteries→arterial insufficiency of lower extremities. Stents and Pentoxifylline are conventional Tx. Vit E does work well for this. Mechanism: hypothesized having to do w/ ↓LDL oxidation or ↓platelet activation

Indications- Vit EIndications- Vit E

1)Gynecological conditions:a. Fibrocystic breast disease (600-800 IU/day): Results have been

conflicting – uncontrolled trials showed benefit, whereas a 2-month double-blind trial showed no effect. Maximal affect after 2-3 cycle of being on E..

b. Premenstrual syndrome: Supplementation with 600 IU/day relieved symptoms of PMS in a double-blind study.

c. Menopausal hot flashes: Supplementation with 400-800 IU/day appears to be occasionally helpful. Improvement has been reported in several uncontrolled trials, whereas no benefit was found in controlled studies. Unesterified tocopherols appear to be more effective than esterified forms of vitamin E (clinical observation). A favorite Tx for hot flashes (esp those w/ Hx of breast CA- may not want to use isoflavones w/ these pts)

1)Dysmenorrhea: Supplementation with 150 IU/day for 2-3 menstrual cycles significantly reduced symptoms compared with placebo (double-blind trial).

1)Gynecological conditions:a. Fibrocystic breast disease (600-800 IU/day): Results have been

conflicting – uncontrolled trials showed benefit, whereas a 2-month double-blind trial showed no effect. Maximal affect after 2-3 cycle of being on E..

b. Premenstrual syndrome: Supplementation with 600 IU/day relieved symptoms of PMS in a double-blind study.

c. Menopausal hot flashes: Supplementation with 400-800 IU/day appears to be occasionally helpful. Improvement has been reported in several uncontrolled trials, whereas no benefit was found in controlled studies. Unesterified tocopherols appear to be more effective than esterified forms of vitamin E (clinical observation). A favorite Tx for hot flashes (esp those w/ Hx of breast CA- may not want to use isoflavones w/ these pts)

1)Dysmenorrhea: Supplementation with 150 IU/day for 2-3 menstrual cycles significantly reduced symptoms compared with placebo (double-blind trial).

Dosage Vit EDosage Vit E

• Dosage: Although clinical benefits have been seen with

as low as 10-50 IU, most physicians recommend doses of

several hundred IU. Safe upper limit has been defined as

1000 IU.

Vitamin E is listed in International Units (IU) and

milligrams.

• Dosage: Although clinical benefits have been seen with

as low as 10-50 IU, most physicians recommend doses of

several hundred IU. Safe upper limit has been defined as

1000 IU.

Vitamin E is listed in International Units (IU) and

milligrams.

Interactions - Vitamin EInteractions - Vitamin E

1)Phenothiazines: Vitamin E (800-1,600 IU/day) reduced the severity of tardive dyskinesia (tics→robert deniro in awakenings) caused by phenothiazines (double-blind trials). Patients with tardive dyskinesia for more than 5 years did not respond. Dr B would recommend this as more of a prevention than for an ongoing issue.

2)Warfarin: An early case report suggesting that vitamin E increases the activity of warfarin has been refuted by a controlled trial. Vit E is not Cx in pts on warfarin. If someone is on a blood thinner and you want to add something that may affect bleeding time you need to monitor bleeding times.

3)Chemotherapy side effects: Vitamin E (300 IU/day) reduced the incidence of cisplatin-induced neurotoxicity. Vitamin E was begun 1-8 days prior to the start of chemotherapy and was continued for 3 months after the end of chemotherapy. In a study in mice, vitamin E did not inhibit the antitumor effect of cisplatin..

4) Iron: Vitamin E and iron exert mutually inhibitory effects.5)Polyunsaturated fatty acids: Administration of polyunsaturated fatty acids

(either omega-6 or omega-3) may increase the requirement for vitamin E. Ignore this interaction→new study refuted this.

6)Other antioxidants: Vitamin E enhances the therapeutic effect of vitamin A, as well as some of the actions of selenium.

1)Phenothiazines: Vitamin E (800-1,600 IU/day) reduced the severity of tardive dyskinesia (tics→robert deniro in awakenings) caused by phenothiazines (double-blind trials). Patients with tardive dyskinesia for more than 5 years did not respond. Dr B would recommend this as more of a prevention than for an ongoing issue.

2)Warfarin: An early case report suggesting that vitamin E increases the activity of warfarin has been refuted by a controlled trial. Vit E is not Cx in pts on warfarin. If someone is on a blood thinner and you want to add something that may affect bleeding time you need to monitor bleeding times.

3)Chemotherapy side effects: Vitamin E (300 IU/day) reduced the incidence of cisplatin-induced neurotoxicity. Vitamin E was begun 1-8 days prior to the start of chemotherapy and was continued for 3 months after the end of chemotherapy. In a study in mice, vitamin E did not inhibit the antitumor effect of cisplatin..

4) Iron: Vitamin E and iron exert mutually inhibitory effects.5)Polyunsaturated fatty acids: Administration of polyunsaturated fatty acids

(either omega-6 or omega-3) may increase the requirement for vitamin E. Ignore this interaction→new study refuted this.

6)Other antioxidants: Vitamin E enhances the therapeutic effect of vitamin A, as well as some of the actions of selenium.

Toxicity - Vit EToxicity - Vit E

• The highest level human studies have used 3200 IU of vitamin E per day. No significant

toxicity has been demonstrated, even at the higher doses. Doses in animal studies

roughly equivalent to a 50,000 IU human doses have been reported to increase bleeding

time. These studies have been occasionally been used as a caution against high dose

vitamin E (see interaction 2 above).

One study showed an increase in rates of infection in elderly people taking 200 IU per day

of vitamin E. Another study showed 600 IU of vitamin E led to a measurable impairment

in glucose tolerance (in contrast to other studies in diabetics).

People taking 400IU/day Vit E found more hemorrhagic strokes and less occlusive

strokes.

Studies looked at Vit E on scar tissue formation→most showed no benefit and one showed that it made the scarring worse→may be due to increased infxn.

• The highest level human studies have used 3200 IU of vitamin E per day. No significant

toxicity has been demonstrated, even at the higher doses. Doses in animal studies

roughly equivalent to a 50,000 IU human doses have been reported to increase bleeding

time. These studies have been occasionally been used as a caution against high dose

vitamin E (see interaction 2 above).

One study showed an increase in rates of infection in elderly people taking 200 IU per day

of vitamin E. Another study showed 600 IU of vitamin E led to a measurable impairment

in glucose tolerance (in contrast to other studies in diabetics).

People taking 400IU/day Vit E found more hemorrhagic strokes and less occlusive

strokes.

Studies looked at Vit E on scar tissue formation→most showed no benefit and one showed that it made the scarring worse→may be due to increased infxn.

Vitamin KVitamin K

• Biochemistry: Vitamin K is necessary to utilize several

of the blood clotting factors. It is also necessary for bone

production. K stands for coagulation (in german). K

dependant clotting factors are 2,7,9,11. Warfarin is an

antagonist for vit K. May need to use vit K in warfarin pts

if they have over dosed on warfarin. INR=figured value

based on bleeding times→generally kept btwn 2-3 to

prevent adverse risk. If INR is >5-6→refer to hospital.

Dietary factors, exercise, hydration can affect INR levels.

↓INR→more clotting. ↑INR→ ↑thinning→↓clotting

• Biochemistry: Vitamin K is necessary to utilize several

of the blood clotting factors. It is also necessary for bone

production. K stands for coagulation (in german). K

dependant clotting factors are 2,7,9,11. Warfarin is an

antagonist for vit K. May need to use vit K in warfarin pts

if they have over dosed on warfarin. INR=figured value

based on bleeding times→generally kept btwn 2-3 to

prevent adverse risk. If INR is >5-6→refer to hospital.

Dietary factors, exercise, hydration can affect INR levels.

↓INR→more clotting. ↑INR→ ↑thinning→↓clotting

Indications - Vitamin KIndications - Vitamin K

1)Blood clotting: Treatment of blood clotting disorders resulting from vitamin K deficiency. Vitamin K can also be used to reverse overdose with coumadin.

1)Prevention and treatment of osteoporosis: Supplementation with 1,000 mcg/day of vitamin K1 reduced urinary calcium loss in postmenopausal women (uncontrolled trials). Supplementation with menatetrenone (vitamin K2; 45 mg/day) reduced bone loss and fracture incidence in postmenopausal women (controlled trials). Vitamin K2 is now available in the United States. Vit K is needed for osteocalcin→protein involved in ossification of bone. High dose vit K shown to increase bone density and decrease Fx. Flouride will increase bone density but may make bone more likely to Fx.

2)Nausea and vomiting of pregnancy: 5 mg/day of vitamin K3 (menadione) plus 25 mg/day of vitamin C relieved symptoms within 3 days in 91% of 70 women (uncontrolled trial). Treatment was continued for an average of 30 days. Vitamin K3 alone was less effective. Vitamin K3 is no longer used, because of potential toxicity; it is not known whether vitamin K1 is effective.

1)Blood clotting: Treatment of blood clotting disorders resulting from vitamin K deficiency. Vitamin K can also be used to reverse overdose with coumadin.

1)Prevention and treatment of osteoporosis: Supplementation with 1,000 mcg/day of vitamin K1 reduced urinary calcium loss in postmenopausal women (uncontrolled trials). Supplementation with menatetrenone (vitamin K2; 45 mg/day) reduced bone loss and fracture incidence in postmenopausal women (controlled trials). Vitamin K2 is now available in the United States. Vit K is needed for osteocalcin→protein involved in ossification of bone. High dose vit K shown to increase bone density and decrease Fx. Flouride will increase bone density but may make bone more likely to Fx.

2)Nausea and vomiting of pregnancy: 5 mg/day of vitamin K3 (menadione) plus 25 mg/day of vitamin C relieved symptoms within 3 days in 91% of 70 women (uncontrolled trial). Treatment was continued for an average of 30 days. Vitamin K3 alone was less effective. Vitamin K3 is no longer used, because of potential toxicity; it is not known whether vitamin K1 is effective.

DOSAGE- Vit KDOSAGE- Vit K

• Dosage: The RDA for vitamin K is 65 mcg/day for adult females and 80 mcg/day for

adult males. Usual supplementary doses are 100-1,000 mcg/day. Larger doses (5-45

mg/day) have been used for specific conditions. Vitamin K1 (phylloquinone) is

synthesized by plants, and vitamin K2 (a family of chemically related molecules) is

synthesized by animals and bacteria. Although all of the forms of vitamin K are known

to have "vitamin K activity," it is not known whether they are all effective for each of the

various conditions listed.

• Dosage: The RDA for vitamin K is 65 mcg/day for adult females and 80 mcg/day for

adult males. Usual supplementary doses are 100-1,000 mcg/day. Larger doses (5-45

mg/day) have been used for specific conditions. Vitamin K1 (phylloquinone) is

synthesized by plants, and vitamin K2 (a family of chemically related molecules) is

synthesized by animals and bacteria. Although all of the forms of vitamin K are known

to have "vitamin K activity," it is not known whether they are all effective for each of the

various conditions listed.

Interactions- Vit KInteractions- Vit K

• Interactions: All forms of vitamin K are strictly

contraindicated with warfarin. Vitamin K containing foods

also should be monitored during anti-coagulant therapies.

• Interactions: All forms of vitamin K are strictly

contraindicated with warfarin. Vitamin K containing foods

also should be monitored during anti-coagulant therapies.

Toxicity - Vit KToxicity - Vit K

• Generally well tolerated at the usual doses. There are no

reports of vitamin K1 toxicity at doses up to 500 times the

RDA. However, additional research is needed to determine

the safety of long-term use of high doses.

• It is important to note that although deficiency of vitamin

K impairs the ability to form blood clots, megadoses do not

increase the likelihood of clot formation.

• Generally well tolerated at the usual doses. There are no

reports of vitamin K1 toxicity at doses up to 500 times the

RDA. However, additional research is needed to determine

the safety of long-term use of high doses.

• It is important to note that although deficiency of vitamin

K impairs the ability to form blood clots, megadoses do not

increase the likelihood of clot formation.

NEXT WEEKNEXT WEEK

• Water Soluble Vitamins• Water Soluble Vitamins