Beta-Carotene: The Controversy Continues

Alternative Medicine Review, Dec, 2000 by Lyn Patrick

9-cis retinoic acid is formed only from 9-cis [Beta]-carotene, while all-trans [Beta]-carotene has been shown to be transformed into only all-trans retinoic acid.[51] The 9-cis isomer of [Beta]-carotene appears to be isomerized in the intestinal mucosa to the all-trans isomer[52] and theoretically, all-trans retinoic acid can be metabolized into 9-cis retinoic acid. Although this has been demonstrated both in vivo and in vitro, this pathway is not well understood and has not been demonstrated in the human gut.[46]

In vitro, algal extracts of Dunaliella containing relatively equal mixtures of cis and trans isomers had a greater ability to prevent methyl-linoleate peroxidation than the synthetic all-trans [Beta]-carotene.[53] The ability of the trans and cis isomers of [Beta]-carotene to prevent lipid peroxidation has also been studied in an animal model.[54] Rats were fed 1 g/kg [Beta]-carotene either in a Dunaliella extract of 75-percent 9-cis [Beta]-carotene or a synthetic all-trans isomer, and both groups were fed oxidized soy oil. Both carotenoid isomers prevented lipid peroxidation to the same extent; however, the trans isomer resulted in a significant depletion of hepatic carotene stores while the 9-cis isomer conserved liver carotene stores comparable to the levels in rats fed fresh soy oil.

As a result of the conflicting data between the cancer-protective effect of dietary carotenoid consumption and the subsequent negative results of supplementation trials using all-trans isomers of [Beta]-carotene, interest in the absorption and biochemistry of the [Beta]-carotene isomers has increased. Research has centered on the absorption and utilization of the three main isomers found in natural sources: all trans, 9-cis, and 13-cis [Beta]-carotene.

Data from absorption studies show clear differences in absorption among the isomeric forms. Multiple studies have compared human absorption of synthetic all-trans [Beta]-carotene with a natural isomeric mix of all-trans and 9-cis [Beta]-carotene from algal sources (Dunaliella species). The ratios of all-trans to 9-cis carotenoids in the different species of Dunaliella vary from 40:60 to 54:37.[13] Consistently in the studies evaluated in Table 1, the levels of serum and plasma all-trans and 9-cis [Beta]-carotenoids were greater after feeding either synthetic all-trans [Beta]-carotene or, in the study by Jensen,[45] raw carrots containing at least 98-percent all-trans [Beta]-carotene compared to an algal extract.

Table 1: Studies of Beta-Carotene Absorption.

Study                      Data

Gaziano, et al.[56]   24 adult M   F for 6 days
                      100 mg synthetic vs. 66 or
                      100 mg algal source
                      (trans/cis ratio=50:50)

Jensen, et al.[45]    16 adult M and F for 7 days
                      24 mg [Beta]-carotene algal source:
                      (trans/cis ratio=40:60)
                      24 mg [Beta]-carotene raw carrot:
                      (98% all-trans)

Johnson, et al.[57]   15 M single dose of 120 mg
                      [Beta]-carotene containing either all-trans
                      [Beta]C or 80% 9-cis [Beta]C/20% all-trans

You, et al.[52]       3 adult M and F single dose
                      1 mg [Beta]-carotene (99.4% cis)-
                      radioactively labeled ([sup.13]C)

Tamai, et al.[58]     30 adult M 60 mg of either:
                      algal [Beta]-carotene
                      (trans/9-cis ratio=50:50) vs.
                      all trans or placebo - 44 weeks

Study                    [Beta]-carotene absorption

Gaziano, et al.[56]   160% increase in plasma [Beta]-carotene
                      with synthetic, all trans form.
                      87% increase in plasma [Beta]-carotene
                      with natural algal form

Jensen, et al.[45]    algal source: serum cis-carotenoid
                      increase 9.6% of total serum
                      [Beta]-carotene
                      carrot source: serum cis-carotenoid:
                      7.1% total serum [Beta]-carotene

Johnson, et al.[57]   all-trans [Beta]C well absorbed in 7 of 15
                      no increase in all-trans [Beta]C with
                      mixture

You, et al.[52]       >95% of 13 C[Beta]-carotene in plasma
                      found as trans isomer (14-52%) and
                      retinol

Tamai, et al.[58]     Levels of both cis (77%) and trans
                      (116%) isomers significantly higher
                      with all-trans [Beta]-carotene

Jensen gave either 207 g raw carrot (24 mg [Beta]-carotene) containing 98-percent all-trans [Beta]-carotene or an algal-source [Beta]-carotene (24 mg from Dunaliella) to 16 healthy adults and serum levels of all-trans and cis [Beta]-carotene were compared after seven days. The absorption of [Beta]-carotene from the raw carrot was greater than from the algae and the rise in serum cis [Beta]-carotene was significantly greater in those fed carrots than those who received algal carotene capsules. Despite the 50:50 trans-to-cis ratio of the algal carotenes, the absorption rate of cis-carotenes in the serum was only 9.6 percent of the rise in total serum [Beta]-carotene level, only slightly more than the rise in the serum level of cis [Beta]-carotene (7.1%) with raw carrot. There was a constant serum trans:cis ratio of 11:1 after Dunaliella-derived [Beta]-carotene ingestion indicating what other researchers have found, a higher ratio of trans to cis isomers in the serum, plasma, and chylomicrons after feeding algal-source [Beta]-carotene.[55] In chylomicrons, the ratio of trans to cis isomers has been shown to be between 10:1 and 50:1 after consumption of 5.6 mmol/kg natural [Beta]-carotene consisting of 54-percent all-trans [Beta]-carotene and 37-percent 9-cis [Beta]-carotene.[46]