So what are scientists saying now about Carotenoids and Vitamin A (Retinoids)? Let's review the data available and examine what lessons may be learned for further plaque eradication and heart protection.
The below researchers from Sweden believe that Vitamin A and Carotenoids have a strong role in preventing restenosis after coronary intervention. And like vitamin D, low blood concentrations of Carotenoids and Vitamin A are statistically correlated to greater ischemic heart disease and coronary events. Additionally, recently published is one of the first studies to show low serum total carotenoids are independent predictors of all-cause 5-y mortality among older women living in the community. The main cause of mortality (14.1%) in the cohort was cardiovascular disease (32.6%). Clearly the advantages for heart protection with these fat-soluble vitamins mirror many of the same spectacular effects witnessed with the other fat-soluble vitamin, the 'D.' (As well as natural E and K2/menaquinones)
- Gidlöf AC, Ocaya P, Krivospitskaya O, Sirsjö A. Vitamin A: a drug for prevention of restenosis/reocclusion after percutaneous coronary intervention? Clin Sci (Lond). 2008 Jan;114(1):19-25. Review. PMID: 18047466
- Gey KF, Moser UK, Jordan P, Stähelin HB, Eichholzer M, Lüdin E. Increased risk of cardiovascular disease at suboptimal plasma concentrations of essential antioxidants: an epidemiological update with special attention to carotene and vitamin C. Am J Clin Nutr. 1993 May;57(5 Suppl):787S-797S. Review. PMID: 8475897 (Please see Figure 2 for IHD vs. Serum Carotene)
- Ray AL, Semba RD, Walston J, Ferrucci L, Cappola AR, Ricks MO, Xue QL, Fried LP. Low serum selenium and total carotenoids predict mortality among older women living in the community: the women's health and aging studies. J Nutr. 2006 Jan;136(1):172-6. PMID: 16365078 (total serum carotenoid concentration 9.1 umol/L associated with longest longevity)
You are already aware that I do love my Soltriol (i.e. vitamin D -- the early nomenclature as it related to its initially discovered solar-related powers). Now after reviewing some of the literature on the incredible anti-inflammatory, heart rhythm stabilizing, and plaque-exterminating effects of Vitamin A and Astaxanthin (a carotenoid, cousin of vitamin A), I am convinced that these dietary components have extremely high heart protective value. Is my heart growing for Vitamin A and its cousin Carotenoid?
Both vitamin D and A receptors are ubiquitious not only throughout the eukaryotic kingdom, but also found in EVERY cell of every eukaryotic cell. Scientists continue to locate these receptors in the most intersting places (like human sperm -- discovered in 2006). These receptors appear to be super-switches for energy production and balance, growth, development, reproduction, survival, and life extension. Thus it may reflect why they are found e-v-e-r-y-w-h-e-r-e.
- Barsony J, Prufer K. Vitamin D receptor and retinoid X receptor interactions in motion. Vitam Horm. 2002;65:345-76. Review. PMID: 12481554
- Bettoun DJ, Burris TP, Houck KA, Buck DW 2nd, Stayrook KR, Khalifa B, Lu J, Chin WW, Nagpal S. Retinoid X receptor is a nonsilent major contributor to vitamin D receptor-mediated transcriptional activation. Mol Endocrinol. 2003 Nov;17(11):2320-8. PMID: 12893883
- Sánchez-Martínez R, Zambrano A, Castillo AI, Aranda A. Vitamin D-dependent recruitment of corepressors to vitamin D/retinoid X receptor heterodimers. Mol Cell Biol. 2008 Mar 24. PMID: 18362166
Severe vitamin A deficiency as you are probably aware is one of the leading causes of global blindness. What does chronic vitamin A deficiency cause? Infertility? Cancer? Skin disorders (ie psoriasis, exczema, acne)? Heart disease?
YES. To all.
Does it sound familiar?
Like Vitamin D, Vitamin A, its derivatives (retinoids) and Beta-carotene and its derivatives (carotenoids) have been shown in human trials to treat and prevent cancers:
--suppresses carcinogenesis of skin, lung, breast, oral, prostate, ovary--acute promyelocytic leukaemia (APL) -- in fact 'cures' APL without a doubt
Vitamin A is used short term at high dose 50,000 IU to 100,000 IU adjunctly to augment cancer therapy as part of core integrative nutraceutical programs (incl natural beta-carotene, high dose vitamin D 25(OH)D 75ng/ml, high dose fish oil (4-20g/day), glutamine, butyrate, etc)
If you want to go fast... go alone.
If you want to go far... go together.
Why is Vitamin A used together with Vitamin D? Why are they found in potent quantities together in nature (ie, fish liver, oily fish, salmon, oysters, trout, catfish, egg yolk, zooplankton, butter, pate, fish eggs/roe/caviar, breastmilk)? All the best foods in life... (breastmilk -- my kids were really into that stuff). Pasture-raised cows indeed produce butterfat brimming with a wealth of cardioprotective vitamins K2, A, D and E! I wonder why??
A synergistic effect has been observed for nearly all benefits studied. This makes absolute sense since they exist co-dependently physically located in the nucleus of our cells.
- Synergistic cardioprotection of Vitamin D3 and retinoic acid protect against hypertrophy of neonatal rat cardiac myocytes induced by endothelin
- Synergistic anti-proliferative effective of vit D derivatives and 9-cis-retinoic acid on neuroblastoma cells
- Synergism between vit D derivative and retinoids on skeletal cells
- Synergistic inhibition of prostate cancer cell lines by vit D analogues and a retinoid
- Synergistic terminal differentiation of leukemia cells by Vitamin D3 and retinoic acid
For heart protection, Li et al demonstrated that Astaxanthin dramatically reduces MMP-3 expression in the plaque found in the thoracic aorta of atheroscleroic rabbits (p<0 .05=".05" activity="activity" and="and" been="been" br="br" de-stabilization="de-stabilization" have="have" high="high" implicated="implicated" in="in" mmps="mmps" of="of" plaque="plaque" rupture.="rupture.">
Li W, et al. Alpha-tocopherol and astaxanthin decrease macrophage infiltration, apoptosis and vulnerability in atheroma of hyperlipidaemic rabbits. J Mol Cell Cardiol. 2004 Nov;37(5):969-78.
Cardioprotective Effects of Astaxanthin (carotenoid)
- Setnikar I, Senin P, Rovati LC. Antiatherosclerotic efficacy of policosanol, red yeast rice extract and astaxanthin in the rabbit. Arzneimittelforschung. 2005;55(6):312-7.
- Aoi W, Naito Y, Sakuma K, Kuchide M, Tokuda H, Maoka T, Toyokuni S, Oka S, Yasuhara M, Yoshikawa T. Astaxanthin limits exercise-induced skeletal and cardiac muscle damage in mice. Antioxid Redox Signal. 2003 Feb;5(1):139-44.
- Gross GJ, Lockwood SF. Acute and chronic administration of disodium disuccinate astaxanthin (Cardax) produces marked cardioprotection in dog hearts. Mol Cell Biochem. 2005 Apr;272(1-2):221-7.
- DA, Lockwood SF, Lucchesi BR. Disodium Disuccinate Astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. J Pharmacol Exp Ther. 2005 Aug;314(2):686-92.
- Hussein G, Goto H, Oda S, Sankawa U, Matsumoto K, Watanabe H. Antihypertensive potential and mechanism of action of astaxanthin: III. Antioxidant and histopathological effects in spontaneously hypertensive rats. Biol Pharm Bull. 2006 Apr;29(4):684-8.
- Iwamoto T, Hosoda K, Hirano R, Kurata H, Matsumoto A, Miki W, Kamiyama M, Itakura H, Yamamoto S, Kondo K. Inhibition of low-density lipoprotein oxidation by astaxanthin. J Atheroscler Thromb. 2000;7(4):216-22. (dose finding study for Astaxanthin in healthy humans -- demonstrated dose related suppression of oxLDL)
- Jacobsson LS, Yuan XM, Ziedén B, Olsson AG. Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits. Atherosclerosis. 2004 Apr;173(2):231-7.
- Hussein G, Nakagawa T, Goto H, Shimada Y, Matsumoto K, Sankawa U, Watanabe H. Astaxanthin ameliorates features of metabolic syndrome in SHR/NDmcr-cp. Life Sci. 2007 Jan 16;80(6):522-9.
- Uchiyama K, Naito Y, Hasegawa G, Nakamura N, Takahashi J, Yoshikawa T. Astaxanthin protects beta-cells against glucose toxicity in diabetic db/db mice. Redox Rep. 2002;7(5):290-3.
- Naito Y, Uchiyama K, Aoi W, Hasegawa G, Nakamura N, Yoshida N, Maoka T, Takahashi J, Yoshikawa T. Prevention of diabetic nephropathy by treatment with astaxanthin in diabetic db/db mice. Biofactors. 2004;20(1):49-59.
- Lee SJ, Bai SK, Lee KS, Namkoong S, Na HJ, Ha KS, Han JA, Yim SV, Chang K, Kwon YG, Lee SK, Kim YM. Astaxanthin inhibits nitric oxide production and inflammatory gene expression by suppressing I(kappa)B kinase-dependent NF-kappaB activation. Mol Cells. 2003 Aug 31;16(1):97-105.
- Murillo E. [Hypercholesterolemic effect of canthaxanthin and astaxanthin in rats]. Arch Latinoam Nutr. 1992 Dec;42(4):409-13. (raises HDL component significantly)
Cardioprotective Effects of Vitamin A(RA=retinoic acid is the carboxylic acid of vitamin A) (All-trans-retinoic acid (ATRA) is the primary active metabolite of vitamin A) (9-Cis retinoic acid, a metabolite of vitamin A, is the most potent ligand of RXR)
- Wu J 1996: Vitamin D3 and retinoic acid protect against hypertrophy of neonatal rat cardiac myocytes induced by endothelin
- Zhou MD 1995: Retinoid-dependent pathways suppress myocardial cell hypertrophy by minimizing alpha-adrenergic receptor-dependent hypertrophy
- Kang, Leaf 1995: All-trans-retinoic acid protects against cardiac arrhythmias induced by ischemia, adrenaline-like stimulants
- de Paiva 2003: Retinoic acid at small physiological doses remodeled damaged heart issue in adult rats
- Wang 2003: All-trans-retinoic acid prevented remodeling in cultured rat cells and cardiac hypertrophy induced by angiotensin II
- Worley JR 2003: 9-cis-retinoic acid prevent MMP-9 in human monocyte-like cells
- de Paiva 2005: Retinoic acid supplementation attenuates ventricular modeling post-myocardial infarction in rats
- Preston 2005: All-trans retinoic acid elicits inhibition of serontonin-induced changes in cultured human smooth muscle cells (took cells from human subjects with idiopathic pulmonary arterial hypertension who often demonstrate low serum levels of RA and 13-cis-RA compared with healthy controls)
- Choudray 2007: All-trans-retinoic acid in pressure overloaded rats (by aortic band) prevented systolic and diastolic dysfunction and change in cardiac structure by inhibiting the rennin-angiotensin system.
- Choudray 2008: All-trans-retinoic acid prevents angiotensin II and mechanical stretch induced ROS generation cardiomyocyte cell death
- Mercader 2006: with retinoic acid remodeling of WAT in mice, increased thermogenesis in skeletal muscle, triggered reduction in body weight, reduction in visceral fat, improved glucose tolerance
Vitamin A (Natural)
- Dose of Vitamin A: 5,000 to 10,000 IU** daily in the morning with food
- Use Natural only
- Side effects: Rare (unless high dose or synthetic analogue and/or vitamin D deficient -- hepatitis, hypertriglyceridemia, osteoporosis, joint aches)
- Food Sources: Bioavailability increases with presence of fat, fiber, protein, acidity, being heated (for vegetables; for fish, least amount of cooking maintains activity). Animal sources include liver and organ meat, red meat, whole fish, fish oils, cod liver oil, egg yolk, butter, dairy products, and breastmilk. Dark green vegetables, yellow and red fruits (excluding citrus) and vegetables, and red palm oil are rich sources of retinoids and carotenoids.
- Teratogenic (with high dose or synthetic analogues) -- Avoid supplementation without MD supervision if pre-conceiving, pregnant.
- **Caveat: Discuss with your physician prior to starting -- If you already at goal for vitamin D 25(OH)D 50 - 80 ng/ml, then consider reducing your vitamin D dose by 25-50% and re-checking the vitamin D status 25(OH)D 6-8 weeks later to verify that the 25(OH)D has not increased excessively (supratherapeutic levels). Both A and D are fat-soluble vitamins, co-factors and synergize each other's respective actions and I believe blood concentrations (like the addition of other steroid nuclear receptor agonists increases Vitamin D blood concentrations, and... vice versa. Yes...The latter has been demonstrated anecdotally. Rare studies also confirm this phenomenon). Therefore, it's prudent to reduce vitamin D supplementation if you begin vitamin A supplementation... and t-r-a-c-k i-t . :)
- Dose of Astaxanthin: 1.5 to 2 mg daily in the morning with food
- Use Natural only
- (Synthetic Astaxanthins are used commercially in farmed salmon, trout and other aquaculture; these fake analogues are apparently made from benzene/petrochemicals; avoid all un-natural vitamins if possible. A synthetic beta-carotene, Lurotin by BASF, was shown to increase cancer, heart attacks, and mortality in clinical human trials.)
- Side effects: Rare (limited human trials but so far none reported). Less joint aches, wrinkles, cancer, H.pylori dyspepsia, infections, male infertility, etc.
- Food sources: Microalgae, yeast, wild salmon (especially wild sockeye), wild rainbow trout, krill, shrimp, shellfish.