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Dr. Berne's Whole Health Support

Dr. Berne's Whole Health Vitamin E Isomers

$28.00

Dr. Berne’s Whole Health Vitamin E Isomers is a unique tocopherol-free, tocotrienols-only product featuring tocotrienols sourced from the annatto tree. Annatto is the richest known source of tocotrienols, containing 100% tocotrienols (90% delta-isomers and 10% gamma-isomers), with no tocopherols.

Dr. Berne’s Whole Health Vitamin E Isomers 150 contains 150 mg per softgel of delta- and gamma-tocotrienols. Commercial vitamin E supplements are typically rich in tocopherols and low or absent in tocotrienols; however, tocotrienol fractions have unique beneficial effects across a variety of tissues that make them desirable for supporting many aspects of health. Research indicates that tocopherols — especially alpha-tocopherols — may interfere with key clinical effects of tocotrienols, so it may be best to take tocotrienols alone, without tocopherols.

Recommended Use: Take 1 softgel per day or as directed by your health-care practitioner.

ALL SALES ARE FINAL - SORRY NO RETURNS OR REFUNDS

 

Regarding eye health

Vitamin E has long been regarded as a beneficial nutrient to support eye health and was included in the original Age‐Related Eye Disease Study (AREDS) and in AREDS2, which also examined other antioxidants, such as lutein and zeaxanthin. AREDS investigated only alpha‐tocopherol, but newer studies suggest that tocotrienols warrant dedicated research. Owing to inhibition of angiogenesis, tocotrienols may have application in improving ocular conditions related to abnormal neovascularization, such as macular degeneration and diabetic retinopathy. Tocotrienol is a potent anti‐angiogenic agent, with delta‐tocotrienol being the most effective.1,2

As a powerful antioxidant, tocotrienol accumulates in the eye to combat cataract development, among the most common eye problems in the aging population.3 Rodent models show that tocotrienol administration delayed the onset and progression of cataracts by reducing lenticular oxidative and nitrosative stress,4 and in diabetic rats, tocotrienol application arrested cataract progression and restored lens transparency to normal.5 (It should be noted, however, that these studies used topically applied tocotrienols through eye drops.  Annatto E protects the lens of the eye, the macula, and supports healthy eye circulation, cornea and eyelid health.

 

The Vitamin E Story

Vitamin E is not a single nutrient, but rather a complex made up of eight distinct compounds: four tocopherols and four tocotrienols. These components have slightly different chemical structures, and these differences impart unique properties that influence their biochemical functions and their effects in the body. Most conventional supplements are typically rich in tocopherols — alpha-tocopherol, in particular — but the tocotrienol fractions have unique effects across a variety of tissues that make them desirable to supplement on their own, without tocopherols.

Rich sources of vitamin E include whole grains, such as wheat (especially wheat germ), rice, barley, oats, corn, select leafy green vegetables, and palm fruit. Most of these foods, however, are higher in tocopherols than tocotrienols.
The richest known source of naturally occurring tocotrienols is annatto, derived from the seeds of a tree native to Latin America. Annatto is virtually free of tocopherols and contains nearly 100% tocotrienols, all in the most potent forms. The tocotrienols in this product are sourced from annatto, so they’re exclusively tocotrienols.

Benefits of Tocotrienols

Tocotrienols have shown impressive effects in supporting cardiovascular health, particularly in regard to supporting healthy cholesterol and triglyceride metabolism. They may also be beneficial for promoting a healthy inflammatory response. Tocotrienols also support healthy blood pressure in relation to their support of healthy blood vessel function.*

Owing to their promotion of normal blood lipid metabolism, tocotrienols may be beneficial for metabolic support related to blood glucose and insulin metabolism. New research also suggests tocotrienols may be a valuable addition to the supplement regimens of those who need nutritional support for strong, healthy bones.

Perhaps the best-known role for the vitamin E complex is that of an antioxidant. Tocopherols have antioxidant effects, but tocotrienols are more potent at protecting against cellular damage from harmful free radicals. The powerful antioxidant function of tocotrienols has been demonstrated in studies of skin and eye health, where damage from oxidation can lead to premature aging of the skin and compromised visual acuity. Abnormal growth of blood vessels in the eyes can also lead to problems with vision. Tocotrienols have been shown to help reduce this issue.*

Why No Tocopherols?

Supplements claiming to contain vitamin E are often only alpha- tocopherol. Although alpha-tocopherol has beneficial effects of its own, it has been shown to interfere with the positive effects of tocotrienols, which also inhibits absorption of tocotrienols and causes them to break down faster. For this reason, it is best to take tocotrienols independently of any other supplements that contain alpha-tocopherol, and it is recommended to separate tocotrienol and tocopherol supplementation by at least 6 hours.

Tocotrienols may be beneficial for:

  • Supporting a healthy inflammatory response
  • Cell protection and improving antioxidant status
  • Supporting healthy cholesterol metabolism
  • Eye and bone health

Vitamin E research has come a long way in recent decades. Vitamin E is not a single nutrient, but rather a complex comprising four tocopherols and four tocotrienols. Each of these components has a different molecular weight and a slightly different chemical structure, which impart distinct properties that influence their biochemical functions. Commercial supplements are typically rich in tocopherols — alpha‐tocopherol, in particular — but the tocotrienol fractions have unique effects across a variety of tissues that make them desirable to supplement alone, without tocopherols.

Rich sources of vitamin E include whole grains, such as wheat (especially the germ), rice, barley, oats, and corn, as well as palm fruit and annatto. Most of these foods, however, are higher in tocopherols than in tocotrienols (T3). The vitamin E in rice, for example, is comprised of 50% tocopherols, 35% delta‐ and gamma‐T3, and 15% alpha‐ and beta‐T3, which are less potent than the delta and gamma forms. Palm is a bit higher in tocotrienols: 25% tocopherols, 25% alpha‐ and beta‐T3, and 50% delta‐ and gamma‐T3. The richest known source of naturally occurring tocotrienols, however, is annatto, which is virtually free of tocopherols and contains 100% tocotrienols (90% delta and 10% gamma).

The tocotrienols in Annatto‐ETM are sourced from annatto, so they are exclusively tocotrienols. This was a deliberate choice by Designs for Health, because research indicates that tocopherols — especially alpha‐tocopherol — interfere with key therapeutic effects of tocotrienols, so it may be best to dose tocotrienols alone, or with 6 hours between tocotrienols and products containing alpha‐tocopherol. (See “Why No Tocopherols?” on page 4.) The tocotrienols in this product are provided as Delta Gold®, a patented tocotrienol formula from American River Nutrition. They are manufactured in the U.S. and have the Generally Recognized as Safe (GRAS) status from the Food and Drug Administration (FDA).

Dyslipidemia and Cardiovascular Health

Tocotrienols enhance the degradation of 3‐hydroxy‐3‐methylglutaryl–coenzyme A (HMG–CoA) reductase, a key enzyme in the mevalonate pathway, by which cholesterol is synthesized.1,2 Animal studies indicate the potency of inhibition of cholesterol synthesis by tocotrienols is: delta > gamma > alpha > beta. Tocopherols are inactive in lowering cholesterol.3 Unlike statin drugs, however, which directly inhibit HMG‐CoA reductase, tocotrienols do not appear to impair synthesis of CoQ10. According to research conducted by prominent vitamin E expert, Barrie Tan, PhD, tocotrienols may reduce cholesterol by 15 to 20% with a concurrent 5% increase in CoQ10, likely owing to increased liver synthesis of CoQ10.4 Delta and gamma‐T3 also block processing of sterol regulatory element‐binding protein, which has implications for potentially reducing triglycerides.

Unlike tocotrienols, tocopherols do not have cholesterol‐lowering effects.1 In fact, the opposite is true: alpha‐tocopherol has been repeatedly shown to attenuate or interfere with the cholesterol‐lowering action of tocotrienols.5 Combinations effective in cholesterol‐lowering consist of 15% or less alpha‐tocopherol and 60% or more gamma‐ and delta‐T3, whereas formulas consisting of 20% or more alpha‐tocopherol and 45% or less gamma‐ and delta‐T3 have been shown to be ineffective. Substantiating these formulating guidelines are clinical studies in which supplements with high alpha‐tocopherol content did not contribute to the lowering of cholesterol,6‐8 whereas supplements containing low amounts of alpha‐tocopherol and high amounts of gamma‐ and delta‐tocotrienol led to a significant decrease in total and LDL cholesterol.9,10‐12

A clinical trial tested the dose‐dependent effects of annatto tocotrienols ranging from 125 mg to 750 mg per day on hypercholesterolemic individuals.9 Results showed that after only 4 weeks, a daily dose of 250 mg decreased total cholesterol by 15%, low‐density lipoprotein (LDL) cholesterol levels by 18%, and triglycerides by 14%. Additionally, cytokines associated with cardiovascular disease and their gene expression (tumor necrosis factor‐α, interleukin [IL]‐2, IL‐4, IL‐6, and IL‐8), were downregulated 39% to 64%.

Inflammation is increasingly recognized as a major driver of cardiovascular disease. In a clinical trial of supplementation with delta‐T3 in hypercholesterolemic subjects, 250 mg of delta‐T3 decreased C‐reactive protein (CRP) and malondialdehyde (MDA) by 40% and 34%, respectively, with a 22% increase in total antioxidant status.13 One of the first steps of atherogenesis is fatty streak formation in arteries, which begins with the adherence of circulating monocytes to the endothelium. Tocotrienols have been shown to reduce cellular adhesion molecule expression and monocytic cell adherence.14,15 In particular, delta‐T3 showed the most profound inhibitory effect compared with tocopherols and other tocotrienol isomers. Delta‐ and gamma‐tocotrienol were 60 and 30 times more potent than alpha‐tocopherol, respectively.16

There may be a role for tocotrienols in hypertension. In hypertensive rats, gamma‐T3 was shown to reduce systolic blood pressure and improve nitric oxide synthase activity, both of which play a critical role in the pathogenesis of essential hypertension.17 In humans, tocotrienols have been shown to increase arterial compliance and reduce blood pressure.18,19

Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease

Rodent models of metabolic syndrome show that tocotrienol supplementation improves insulin sensitivity and reduces triglycerides, adipocyte size, abdominal adiposity, and liver fat deposition.20,21 Human studies using rice bran extracts (>90% tocotrienols) reduced hyperglycemia, glycosylated hemoglobin, and hyperlipidemia in subjects with both type 1 and type 2 diabetes.22 Within 60 days, tocotrienol supplementation was shown to decrease total cholesterol and LDL cholesterol by 30% and 42%, respectively.23 When taken apart from alpha‐tocopherol, tocotrienols were shown to lower total cholesterol, LDLs, and triglycerides 15% to 20%.9 Moreover, tocotrienols also lowered CRP and other inflammatory markers by 35% to 60%.13

Non‐alcoholic fatty liver disease (NAFLD) is a growing epidemic and is closely related to metabolic syndrome and insulin resistance. A double‐blind, randomized controlled trial among 71 subjects showed that with NAFLD, 12 weeks of supplementation with delta‐T3 resulted in significant improvements in biomarkers of hepatic stress, including a 15% to 16% reduction in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), an 11% decrease in triglycerides, a 14% reduction in malondialdehyde (MDA), and an 18% decrease in high sensitivity CRP.24 (However, ultrasound examination revealed no improvement in the hepatic steatosis.)

Antioxidant Capacity

Antioxidants are abundant in the food supply, but vitamin E is uniquely shaped to reside within cell membranes to protect the integrity of the structural lipids. In this regard, tocotrienols were shown to be about 50 times more potent than tocopherols.25 The antioxidant efficiency of tocotrienols was evaluated as the ability of the compounds to inhibit lipid peroxidation and reactive oxygen species production. Delta‐tocotrienol was found to have the greatest antioxidant properties among the tocotrienol isomers.26 In lipid oxygen radical absorbance capacities (ORAC) studies, delta‐ and gamma‐tocotrienols had the highest antioxidant value of all vitamin E isomers at 5.5 and 3 times the potency of alpha‐tocopherol, respectively.27

Skin and Eye Health

Promising research indicates that tocotrienols may help reduce the adverse effects of UV‐irradiation of the skin and UV‐induced melanogenesis.28,29‐31 Tocotrienols may also have a role in improving wound healing and fending off skin infections. In methicillin‐resistant Staphylococcus aureus (MRSA)‐infected mice, given alone, tocotrienol reduced bacterial load by a factor of 10, and antibiotics alone by 1,000 times. In combination, however, tocotrienols and daptomycin reduced bacterial load by 10,000 times, suggesting a highly synergistic effect between the two.32 This synergy is believed to be due to tocotrienols enhancing the activity of natural killer cells.

Regarding eye health, vitamin E has long been regarded as a beneficial nutrient to support eye health and was included in the original Age‐Related Eye Disease Study (AREDS) and in AREDS2, which also examined other antioxidants, such as lutein and zeaxanthin. AREDS investigated only alpha‐tocopherol, but newer studies suggest that tocotrienols warrant dedicated research. Owing to inhibition of angiogenesis, tocotrienols may have application in improving ocular conditions related to abnormal neovascularization, such as macular degeneration and diabetic retinopathy. Tocotrienol is a potent anti‐angiogenic agent, with delta‐tocotrienol being the most effective.33, 34

As a powerful antioxidant, tocotrienol accumulates in the eye to combat cataract development, among the most common eye problems in the aging population.35 Rodent models show that tocotrienol administration delayed the onset and progression of cataracts by reducing lenticular oxidative and nitrosative stress,36 and in diabetic rats, tocotrienol application arrested cataract progression and restored lens transparency to normal.37 (It should be noted, however, that these studies used topically applied tocotrienols through eye drops.)

Chemoprotection

Given at higher doses, tocotrienols have shown impressive effects across a range of cancers, including breast, prostate, colon, and pancreatic cancers, and melanoma. There are several possible mechanisms of action for tocotrienols as adjuncts to conventional cancer therapies. Among these are inhibition of angiogenesis, vascular endothelial growth factor,38,39 and induction of apoptosis through the caspase‐3 pathways.40 Tocotrienols, but not tocopherols, and in particular, not alpha‐tocopherol, have been shown repeatedly to inhibit proliferation and induce cancer cell death, and cells with the greatest degree of malignancy appear to be the most sensitive to the apoptotic actions of tocotrienol.40‐42

Bone Health

Vitamin E tocotrienols are being explored for applications beyond their more traditional uses for lipid management, cardiovascular health, and antioxidant status. Bone health is one of these new areas, with many pre‐clinical studies already having shown promise for supporting stronger bones.43‐45 A double‐blind, placebo‐controlled trial showed that, among post‐menopausal women with osteopenia, compared to a placebo, showed that tocopherol‐free tocotrienols administered at two different dosages (300 mg/day and 600 mg/day, respectively) for 12 weeks resulted in decreased bone resorption and improved bone turnover rate.48 Osteoporosis is not solely a women’s issue. Men are not immune to bone loss as they age, and bone loss may also be an undesirable side‐effect of androgen deprivation therapies. Rodent models of this scenario show that supplementation with annatto tocotrienols resulted in significantly higher bone volume, calcium content, trabecular thickness, and improved biomechanical strength of the femur.49,50

Other osteopenic rat models show that tocotrienols improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture.46 Metabolic syndrome and type 2 diabetes increase risk for osteoporosis, likely owing to systemic hormonal alterations and inflammatory processes. A rodent model showed that supplementation with annatto tocotrienols (60 mg/kg and 100 mg/kg) improved bone strength and trabecular bone microstructure and increased osteoclast number in male rats with metabolic syndrome induced by a high‐carbohydrate, high‐fat diet.51 Along with these improvements in bone health, annatto tocotrienol supplementation also resulted in improvements in several metabolic syndrome parameters, including decreased triglycerides, blood pressure, and fasting glucose. A separate rodent model had similar findings: in male mice with diet‐induced type 2 diabetes, supplementation with annatto tocotrienols (400 mg/kg and 1,600 mg/kg) for 14 weeks resulted in increased trabecular bone volume and cortical thickness, with increased markers of bone formation and decreased markers of bone resorption.52 Additionally, the tocotrienol supplemented mice also had a lower area under the curve for glucose and insulin. Notably, these improvements were greater than those seen in a separate group of diabetic mice treated with metformin (200 mg/kg).

It is believed that tocotrienols may upregulate antioxidant defenses in osteoclasts and “indirectly act against free radical signaling essential in osteoclastogenesis.”53 It is worth noting that alpha‐tocopherol, the most common vitamin E subfraction in conventional supplements, may have adverse effects on bone formation, partly due to interference with the “anabolic effect” of gamma‐tocopherol on the bone.54

Why No Tocopherols?

Alpha‐tocopherol compromises several of the beneficial effects of tocotrienols. For example, it attenuates their cholesterol and triglyceride‐reducing effects,5,55,56 lowers their antioxidant capacity,57 attenuates cancer cell inhibition,58,59 blocks absorption of tocotrienols, and induces their catabolism,60‐64 and prevents adipose and liver storage of tocotrienols.55

References

Annatto‑E™

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  2. Song BL, DeBose‑Boyd RA. Insig‑dependent ubiquitination and degradation of 3‑hydroxy‑3‑methylglutaryl coenzyme a reductase stimulated by delta‑ and gamma‑tocotrienols. J Biol Chem. 2006;281:25054‑25061. doi:10.1074/jbc.M605575200.
  3. Yu SG, Thomas AM, Gapor A, Tan B, Qureshi N, Qureshi AA. Dose‑response impact of various tocotrienols on serum lipid parameters in 5‑week‑old female chickens. Lipids. 2006;41(5):453‑461. doi:10.1007/s11745‑006‑5119‑1.
  4. Tan B, Mueller AM. Tocotrienols in cardiometabolic diseases. In: Watson R, Preedy V, eds. Tocotrienols: Vitamin E Beyond Tocopherol. Boca Raton, FL: AOCS/CRC Press; 2008:257‑273.
  5. Qureshi AA, Pearce BC, Nor RM, Gapor A, Peterson DM, Elson CE. Dietary alpha‑tocopherol attenuates the impact of gamma‑tocotrienol on hepatic 3‑ hydroxy‑3‑methylglutaryl coenzyme A reductase activity in chickens. J Nutr. 1996;126(2): 389‑394. doi:10.1093/jn/126.2.389.
  6. Mensink RP, van Houwelingen AC, Kromhout D, Hornstra G. A vitamin E concentrate rich in tocotrienols had no effect on serum lipids, lipoproteins, or platelet function in men with mildly elevated serum lipid concentrations. Am J Clin Nutr. 1999;69(2):213‑219. doi.org/10.1093/ajcn/69.2.213.
  7. Mustad VA, Smith CA, Ruey PP, Edens NK, DeMichele SD. Supplementation with 3 compositionally different tocotrienol supplements does not improve cardiovascular disease risk factors in men and women with hypercholesterolemia. Am J Clin Nutr. 2002;76(6):1237‑1243. doi: 10.1093/ajcn/76.6.1237.
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  9. Qureshi AA, Dilshad AK, Wajiha M, Qureshi N. Dose‑dependent modulation of lipid parameters, cytokines, and RNA by delta‑ tocotrienol in hypercholesterolemic subjects restricted to AHA Step‑1 diet. Br J Med Med Res. 2015;6(4):351‑366. doi.org/10.9734/BJMMR/2015/13820.
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  13. Qureshi AA, Khan DA, Mahjabeen W, Trias AM, Silswal N, Quereshi N. Impact of delta‑tocotrienol on inflammatory biomarkers and oxidative stress in hypercholesterolemic subjects. J Clin Exp Cardiolog. 2015;6(4): 1000367. doi:10.4172/2155‑9880.1000367.
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  16. Naito Y, Shimozawa M, Kuroda M. Tocotrienols reduce 25‑hydroxycholesterol‑induced monocyte‑endothelial cell interaction by inhibiting the surface expression of adhesion molecules. Atherosclerosis. 2005;180(1):19‑25. doi:10.1016/j.atherosclerosis.2004.11.017
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  19. Rasool AH, Yuen KH, Yusoff K, Wong AR, Rahman ARA. Dose dependent elevation of plasma tocotrienol levels and its effect on arterial compliance, plasma total antioxidant status, and lipid profile in healthy humans supplemented with tocotrienol rich vitamin E. J Nutr Sci Vitaminol (Tokyo). 2006;52(6):473‑478. doi:10.3177/jnsv.52.473.doi:10.3177/jnsv.52.473.
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  28. Traber MG, Podda M, Weber C, Thiele J, Rallis TM, Packer L. Diet‑derived and topically applied tocotrienols accumulate in skin and protect the tissue against ultraviolet light‑induced oxidative stress. Asia Pac J Clin Nutr. 1997;6(1):63‑67.
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  31. Yap WN, et al. Gamma‑ and delta‑tocotrienols inhibit cutaneous melanosis (hallmark of melanoma) by suppressing constitutive and UV‑induced tyrosinase activation. Presented at the 102nd Annual Meeting of the American Association for Cancer Research. Orlando, FL: 2011.
  32. Pierpaoli E, Orlando F, Cironi O, Simonetti O, Giacometti A, Provinciali M. Supplementation with tocotrienols from Bixa orellana improves the in vivo efficacy of daptomycin against methicillin‑resistant Staphylococcus aureus in a mouse model of infected wound. Phytomedicine. 2017;36:50‑53. doi:10.1016/j.phymed.2017.09.011.
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  35. Tanito M, Itoh N, Yoshida Y, Hayakawa M, Ohira A, Niki E. Distribution of tocopherols and tocotrienols to rat ocular tissues after topicalophthalmic administration. Lipids. 2004;39(5):469‑474. doi:10.1007/s11745‑004‑1252‑0.
  36. Abdul Nasir NA. Agarwal R, Vasudevan S, Tripathy M, Alyautdin R, Ismail NM. Effects of topically applied tocotrienol on cataractogenesis and lens redox status in galactosemic rats. Mol Vis. 2014;20:822‑835.
  37. Abdul Nasir NA, Agarwal R, Kadir SHSA, et al. Reduction of oxidative‑nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin‑induced diabetic rats. PLoS One. 2017;12(3):e0174542.
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  39. Nakagawa K, Eitsuka T, Inokuchi H, Miyazawa T, et al. DNA chip analysis of comprehensive food function: inhibition of angiogenesis and telomerase activity with unsaturated vitamin E, tocotrienol. Biofactors. 2004;21(1‑4):5‑10. doi.org/10.1002/biof.552210102.
  40. Sylvester P, Theriault A. Role of tocotrienols in the prevention of cardiovascular disease and breast cancer. Curr Top Nutraceutical Res. 2003;1(2):121‑136.
  41. Wada S, Satomi Y, Murakoshi M, Noguchi N, Yoshikawa T, Nishino H. Tumor suppressive effects of tocotrienol in vivo and in vitro. Cancer Lett. 2005;229(2):181‑91. doi:10.1016/j.canlet.2005.06.036.
  42. Yano Y, Satoh, H, Fukumoto K, et al . Induction of cytotoxicity in human lung adenocarcinoma cells by 6‑O‑carboxypropyl‑alpha‑ tocotrienol, a redox‑silent derivative of alpha‑tocotrienol. Int J Cancer. 2005;115(5):839‑846. doi:10.1002/ijc.20809.
  43. Chin KY, Abdul‑Majeed S, Mohamed N, Ima‑Nirwana S. The effects of tocotrienol and lovastatin co‑supplementation on bone dynamic histomorphometry and bone morphogenetic protein‑2 expression in rats with estrogen deficiency. Nutrients. 2017;9(2):143. doi:10.3390/nu9020143.
  44. Chin KY, Gengatharan D, Nasru FSM, et al. The effects of annatto tocotrienol on bone biomechanical strength and bone calcium content in an animal model of osteoporosis due to testosterone deficiency. Nutrients. 2016;8(12):80‑8. doi:10.3390/nu8120808.
  45. Chin KY, Ima‑Nirwana S. Effects of annatto‑derived tocotrienol supplementation on osteoporosis induced by testosterone deficiency in rats. Clin Interv Aging. 2014;9:1247‑1259. doi:10.2147/CIA.S67016.
  46. Chin KY, Ima‑Nirwana S. The biological effects of tocotrienol on bone: a review on evidence from rodent models. Drug Des Devel Ther. 2015;9:2049‑2061. doi:10.2147/DDDT.S79660.
  47. Shen CL, Klein A, Chin K‑Y, et al. Tocotrienols for bone health: a translational approach. Ann N Y Acad Sci. 2017;1401(1):150‑165. doi:10.1111/nyas.13449.
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Dr. Berne's Whole Health Vitamin E Isomers

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